Several factors contribute to the decision to discontinue
anti-TNF drugs in IBD patients once remission has been achieved,
including the cost of the medications, the serious side effects,
and the outcome following elective withdrawal.

Dr. Casanova and colleagues sought to determine the risk of
relapse after discontinuation of anti-TNF therapy, to identify
the factors associated with relapse, and to evaluate the outcome
after retreatment with the same anti-TNF in those who relapsed.

Their retrospective study included 731 patients with Crohn's
disease (CD) and 324 patients with ulcerative colitis (UC) who
were followed up a median 19 months after discontinuation of
anti-TNF drugs. All had achieved clinical remission.

Relapse occurred at the rate of 18% per patient-year after
discontinuation of anti-TNF therapy, with cumulative relapse
rates of 15% at six months, 24% at one year, 38% at two years,
46% as three years, and 56% at five years.

The incidence of relapse was nonsignificantly higher in CD
patients (19% per patient-year) than in UC patients (17% per
patient-year), but type of IBD was not associated with the risk
of relapse.

Relapse rates were significantly higher among patients who
did not continue treatment with immunomodulators (26% per
patient-year) than among those who did (17% per patient-year),
the team reports in The American Journal of Gastroenterology,
online December 13.

Independent predictors of a higher risk of relapse included
treatment with adalimumab versus infliximab, elective
discontinuation versus discontinuation as part of a top-down
strategy, and discontinuation because of adverse events versus
discontinuation as part of a top-down strategy.

Treatment with immunomodulators after discontinuation and
older age at discontinuation were associated with a lower risk
of relapse.

After relapse, 69% of patients were retreated with the same
anti-TNF drug, 28% received another drug, and 3% underwent
surgery.

Clinical remission was achieved at the end of follow-up by
79% of patients retreated with infliximab and 69% of patients
retreated with adalimumab. Clinical remission was achieved less
frequently by patients who restarted anti-TNF as monotherapy
than by those who restarted anti-TNF combined with
immunomodulators (68% vs. 78%, p=0.08).

Only 11% of patients retreated with an anti-TNF drug
experienced adverse events, and most of these were infusion
reactions.

"Discontinuation of anti-TNF therapy should be considered in
a selected group of patients," Dr. Casanova said. "However, it
cannot be universally recommended. However, some patients can
stop anti-TNF therapy safely and remain in remission for long
periods."

"We think that the decision whether to continue or not with
an anti-TNF should be taken on an individual basis," she said.
"Randomized controlled trials are necessary to identify the
factors associated with the risk of relapse."

"Another important message is that, although the retreatment
with the same anti-TNF drug in patients who relapse after the
initial withdrawal has been reported to be apparently successful
and safe, in our study, 25% of the retreated patients did not
achieved clinical remission," Dr. Casanova said. "For this
reason, we strongly recommend that the potential consequences of
discontinuing the therapy should be always discussed with the
patient."

Dr. Martin Bortlik from Univerzity Karlovy in Prague, Czech
Republic, who recently reported relapse rates of about 50%
within two years after discontinuation of anti-TNF by IBD
patients, told Reuters Health by email, "In my opinion, the main
message is still the same: if really not necessary, dont stop
the effective and well-tolerated anti-TNF therapy."

"Of course, patients sometimes ask for treatment
discontinuation, but it is the job of their gastroenterologist
to provide the patient with correct information," he said. "And
such information should stress that half of them will suffer
from relapse within next 2-3 years, and it is still extremely
difficult to predict which patient is in high or low risk of
relapse."

"I'd like to emphasize the importance of protective effect
of immunosuppressive medication for prolongation of remission
once anti-TNF therapy has been stopped," Dr. Bortlik said. "It
seems especially important in Crohns disease patients where
mesalamine is ineffective and no other medication is thus
available. Therefore, I'd never stop biologic therapy
(electively) in a patient not tolerating thiopurines or
methotrexate."

"The other point is that patients who relapse should start
with the same drug that was previously discontinued," he added.
"It is relatively safe (though the risk of allergic reaction to
infliximab is definitely increased), and it also seems to be
effective in majority of patients. Switching to another drug
should be attempted only if restart is not effective, or adverse
event (mostly allergy) occurs."

The study had no funding. Several authors, including Dr.
Casanova, reported financial ties to companies marketing TNF
blockers.